An emerging PB2-627 polymorphism increases the zoonotic risk of avian influenza virus by overcoming ANP32 host restriction in mammalian and avian hosts.

ABSTRACT: Alterations in the PB2-627 domain of avian influenza virus (AIV) can potentially increase the risk of cross-host species infections in humans and mammals. Recently, there has been a rise in human cases of AIV infections without the presence of the known mammalian determinant PB2-E627K. Here, we identified a variant, PB2-627V, which has evolved in poultry and has contributed to the increase in human AIV infections. By screening global PB2 sequences, we discovered a new independent cluster of PB2-627V that emerged in the 2010s, prevalent in avian, mammalian, and human AIV isolates, including those of H9N2, H7N9, H3N8, 2.3.4.4b H5N1, and other subtypes. We functionally assessed its host adaptation, fitness, and transmissibility across three subtypes of AIVs (H9N2, H7N9, and H3N8) in different

SUBMITTER: Guo Y 

PROVIDER: S-EPMC12455948 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature